Method and apparatus for closed-loop deep brain stimulation in treating neurological diseases

ABSTRACT

A system that incorporates teachings of the present disclosure may include, for example, implanted deep brain stimulation electrodes, a stimulation sequence pulse generator, one or more implanted sensors for collecting data associated with one or more electrical signal from the vicinity of the site where stimulation is applied by the stimulation electrodes, and one or more noninvasive surface EMG electrodes to be attached to the patient&#39;s skin, say, on certain limbs and which may incorporate a wireless transmitter microchip, and a controller. The controller may incorporate one or more wireless receiver microchips to receive inputs from the sensors. It may also have wire input, if placed under the skin of the skull, for inputs from the implanted sensors. It will incorporate a signal processor to process and coordinate the sensed data from the various sensors and to predict the timing for its output commands. The controller also incorporates a decision element to produce a control output to be sent by wire or wireless to the stimulation sequence generator and which may be an on-off command. The signal processor will also discriminate between tremors and intentional movements in the EMG signals utilizing the EMG spectrum. An electronic switch device may be incorporated to allow the implanted electrodes to switch between serving as stimulation electrodes and voltage sensors, thus eliminating the need to implant any separate sensing electrodes. Alternatively, only noninvasive EMG sensing may be employed for closed-loop control.

I claim priority of my Provisional Patent Application No. 61/195,527 filed on Oct. 9, 1008 (confirmation #8444)

FIELD OF THE DISCLOSURE

The present disclosure relates generally to neurological disorders, and more specifically to a method and an apparatus for managing a neurological disorder by deep brain stimulation in closed loop continuously responsive to measurements from the patient in real time.

BACKGROUND

Neurological disorders such as Parkinson's disease can be a chronic, progressive neurodegenerative movement disorder whose primary symptoms include tremors, rigidity, slow movement, poor balance and difficulty walking and in speech. When a person has Parkinson's disease, his/her dopamine-producing cells in the brain begin to die. Dopamine is responsible for sending information to the parts of the brain that control movement and coordination. Hence, as the amount of dopamine produced decreases, messages from the brain directing the body how and when to move are delivered in a slower fashion, leaving a person incapable of initiating and controlling movements in a normal way.

Deep Brain Stimulation (DBS) is a surgical therapy for movement disorders that represents an advancement in the treatment of Parkinson over the last 50 years. DBS uses a surgically implanted, battery-operated thin neuron-stimulator to reverse in large part the abnormal function of the brain tissue in the region of the stimulating electrode.

Commercially available DBS systems typically include a neuron-stimulator, an extension, and a lead. The neuron-stimulator is placed under skin operating as a battery powered electrical impulse generator implanted in the abdomen. The extension is a wire also placed under the skin (from the head, down the neck, to the abdomen) to bring the signals generated by neuron-stimulator to the lead. The lead is an insulated coiled wire with four electrodes implanted deeply in the brain to release the electrical impulse. Presently DBS devices operate only in open loop, namely, they are not continuously responsive to patient's status at a given instance of time but are fixed once the DBS electrodes are surgically implanted.

INNOVATIVE ASPECTS OF THE PRESENT INVENTION

Achieving closed-loop control of DBS where control is continuously responsive to measurements at any given time, using noninvasive surface EMG sensors which sense integrated motor-neuron activity in the vicinity of the electrode through the skin (say, at muscles and limbs including facial muscles, fingers, and vocal cord) and/or implanted sensors.

In preferred realizations of this invention, processing of the data obtained from said sensors and the resulting control decision and control command signals are also performed in a noninvasive manner, these control commands being transmitted by wireless to the implanted device.

In some realization of this invention, measurements of patient's status are solely obtained from sensors that are noninvasive.

In preferred realizations of the present invention, signal processing involves prediction of time of next tremor and detecting and subsequent filtering out of desirable movements.

In realizations as in [0007], sensing and control are then applicable to most existing DBS systems and do not require redesign of presently implanted DBS systems except for installing a miniature wireless receiver.

In some realizations, the stimulating electrode serves also as a sensing electrode, as is accomplished via electronic switching of connection and of impedance, to eliminate need for a separately implanted sensing electrode in the stimulated site of the patient's brain.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic of the Closed Loop Deep-Brain Stimulator

FIG. 2 describes the functions of the electronic switch (ESW)

FIG. 3 describes the EMG electrodes (EMGE) assembly with the wireless transmitter chip (WTM)

FIG. 4 is a schematic of the Closed-Loop Stimulator using only EMGE sensors

DETAILED DESCRIPTION

An embodiment of the present disclosure entails:

A stimulation signal sequence generating system and device (SSG) 101 which generates an train of impulses (TI) 102 that are applied to implanted deep-brain stimulation electrodes (IDSTE) 103 for the purpose of DBS. See FIG. 1.

Clinical testing of Parkinson Disease (PD) patients has shown that after a period T of several seconds, over which stimulation is applied and where tremors and other PD symptoms are suppressed, when stimulation is stopped, there is an interval V over which abnormal symptoms return, where V is also of the order of a few seconds, often approaching T above. Reaching that point can be detected by either sensory electrodes (ISE) implanted in the vicinity of where stimulation is being applied (in the CNS), or by minute changes in parameters derived from surface EMG signals sensed by surface (non-invasive) EMG (electro-myographic) skin-electrodes (EMGE) 104 on certain muscles, say, on the patient's wrist. The start-times and end-times of intervals T and V can be detected via the processing of data from surface-EMG sensors and/or implanted deep brain sensors (IDSE) 105 as discussed below. See FIG. 1.

The invention incorporates a DBS system with a feedback controller device (FCD) 106 to detect the reaching of the critical levels for starting and stopping of stimulation as above, which consists of an implanted deep brain sensory electrode (IDSE) 105 implanted in the vicinity of where DBS is being applied and/or noninvasive surface EMG skin electrodes (EMGE) 104 attached to certain of the patient's muscles (at certain limbs, or other muscles). See FIG. 1.

The above IDSE 105 and EMGE 104 electrodes send their sensory signals to a signal processing device (SP) 107, where the signal parameters are extracted (say as in Ch 5 of: D. Graupe, Time Series Analysis, Identification and Adaptive Filtering, 2^(nd) edition, Krieger Publ. Co., 1989, or by using wavelet transforms as in RM Rao and AS Bopardikar, Wavelet Transforms, Addison Wesley, 1998) which allow prediction of eventual return of symptoms such as tremors before they actually occur and the detection and filtering of normal and desirable movements of the patient to discriminate signal parameters due to these from undesirable symptoms such as tremors, say incorporating artificial neural network algorithms as in D. Graupe, Principles of Artificial Neural Networks, 2^(nd) Edition, World Scientific, 2007, and where a threshold-decision and prediction algorithm determines that another train of stimulation signals is to be applied. See FIG. 1.

The SP device 107 of [00019] is part of the controller device (FCD) 106 of [00018] where, on the basis of the prediction and movement discrimination performed in the SP 107, an on-off control command (CC) 108 is sent from the control-and-decision device CDD 110 of the FCD 106 to a DBS sequence generator (SSG) 101 of [00015], to start and stop DBS stimulation. See FIG. 1.

The SSG 101 generates a DBS stimulation sequence and sends it to the implanted DBS stimulation electrodes (IDSTE) 103 in accordance with the CC 108 of [00019] above. See FIG. 1.

The IDSE 105 of [00016] and the IDSTE 103 of [00015] are physically the same electrode, while performing two functions, namely, sensing (IDSE) 105 and stimulation (IDSTE) 103, as determined by an electronic switch (ESW) 109 which may be an optical switch, noting that stimulation pulses (the pulse-width) last only approximately 50 to 100 microseconds while the interval between these pulses is of the order of 5 to 7 milliseconds, namely 5000 to 7000 microseconds (i.e., stimulation pulse rate is approximately 150 to 200 pulses per second). Hence, the “idle time” between two successive stimuli last approximately 99% of the inter-pulse interval and is available for sensing. The ESW 109 may be housed in the SSG 101. See FIG. 1.

The ESW 109 switches the implanted stimulation electrode (IDTSE) 103 between sending a stimulation pulse from the SSG 101, namely serving as IDSTE 103 and serving as sensor of the voltage at the vicinity of where stimulation is being applied, namely, serving as IDSE 105, thus sending its information to the SP 107 that is located in the FCD 106. See FIG. 1. It does so at usually predetermined fixed intervals, based on the actual pulse width and pulse rate of any given DBS system.

ESW 109 also serves to switch impedances between the one needed for stimulation 201and the impedance needed for sensing 202. See FIG. 2.

The EMGE electrodes 104 may incorporate a wireless transmitter microchip (WTM) 301 to transmit the sensed information to a signal processing and control subsystem that is incorporated in the FCD 106. See FIG. 3.

The above would result in facilitating the application of DBS only when needed, rather then applying DBS continuously (until the physician stops it in a clinical session), as is the present practice. This will avoid overstimulation and protecting the patient from possible side effects due to unnecessarily prolonged stimulation in terms of applying a dose of electrical charge to the stimulated site that is higher than needed.

By our invention, effective stimulation time may be reduced (by our simulation results) by a factor of 2 or better. Furthermore, battery drainage will be reduced by the same factor. We comment that T and modulation levels are determined to maximize the mean ratio of V/T, noting that T and V change as determined by the controller.

By our invention, when no implanted sensors are employed, namely, when sensing is only via EMG electrodes, then closed-loop DBS requires only noninvasive sensing (See FIG. 4). It can then operate with conventional open-loop DBS system, to which only noninvasive sensing electrodes are added as is a noninvasive addition of an SP 107 device or algorithm to an existing on-off controller that is usually noninvasive too. If however, invasive (implanted) sensors (IDSE) 105 are incorporated, still, no additional sensing electrode need to be implanted, since switching and impedance matching allow using the stimulation electrode 103 to also serve as sensor. 

1. A device to apply deep brain stimulation (DBS) to persons with neurological disorders including Parkinson disease and other neurological tremors, comprising one or more implanted electrodes, a stimulation sequence generator device, a controller device and one or more sensor devices which may all be noninvasive and where stimulation is applied over a period of T seconds after which it is interrupted for a period of V seconds, where the durations of T and of V are variable and are each individually determined by a feedback controller system or device, denoted as the controller, on the basis of input from one or more sensing systems or devices, that restarts stimulation over another round lasting for another T seconds, where T is reset as determined by the controller, using same pulse-amplitude pulse-width and pulse-rate parameters as in the previous with round of stimulation, and where this new round of T seconds of stimulation is interrupted again by the controller for another different V seconds until being restarted by the controller system or device, and where the cycles of stimulation and subsequent interruption are repeated again and again, and where the controller system or device restarts stimulation via a decision algorithm or threshold device which serves to determine that stimulation should be renewed in accordance with data it receives from one or more sensing devices which may be noninvasive surface-EMG electrodes attached to the skin of the patient being stimulated and which may also include an voltage sensor to sense the electrical activity in the vicinity of the site that is stimulated by DBS, and where this information is being processed by a signal processing sub-device that is part of the controller device, prior to being fed to the decision algorithm or device and where decision to restart a new round of stimulation is made a predictor sub-system of said signal processor to avoid the abnormal tremors and/or other motor-effects on the patient.
 2. A device as in claim 1, where the analysis of the surface-EMG signal, when employed in the signal processing sub-system or sub-device, is in terms of extracting surface-EMG parameters of that signal.
 3. As in claim 2, where surface-EMG parameters are dynamic time series parameters of the stochastic surface-EMG such as Autoregressive model parameters or ARMA (autoregressive and moving average) parameters or wavelet model parameters or their equivalents and which may serve for prediction over a short time span.
 4. As in claim 3, where the predictor of signal processing sub system or sub-device compensates for the time difference between any neural firing and tremor detected by the EMG sensor.
 5. As in claim 4, where compensation is predictive such that stimulation is re-started at every stimulation cycle slightly, say, a few seconds before tremors have been predicted to occur by the predictor that is incorporated in the signal processing sub-system.
 6. As in claim 1, where a decision algorithm of the predictor determines that a pre-determined threshold-level in the signal has been reached at the implanted sensing electrodes, or in parameters extracted by the signal processing algorithm and its prediction (predictor) sub-system from that signal and which has been determined to be one beyond which abnormal effects of the neurological disorder re-appear unless stimulation is restarted, this threshold level being adjustable by the responsible physician.
 7. As in claim 1, where the decision algorithm detects a pre-determined threshold-level in the signal detected by the surface raw-EMG electrodes or in parameters extracted by the signal processing algorithm from that signal, and which has been determined to be one beyond which abnormal effects of the neurological disorder re-appear unless stimulation is restarted, this threshold level being adjustable by the responsible physician.
 8. As in claim 1 or 2 or 3 or 4 and or 5 or 6 or 7, which employs no implanted sensors.
 9. As in claim 1 or 8, where EMG control is replaced by acceleration sensors.
 10. As in claim 1 or 8, where noninvasive sensor incorporates a wireless transmitter chip and where the controller incorporates a wireless receiver chip.
 11. As in claim 1, where an electronic switching device, which may be an optical switch, is incorporated to connect the stimulation sequence generator device with the implanted electrodes in order that a single implanted electrode can be switched from serving as voltage sensors to serving as implanted stimulation electrode, where this sharing is accomplished by the electronic switch device which switches between sending stimulation pulses to the implanted electrode from just before the beginning of the stimulation pulse and until just after the end of the pulse, and then switching to allow the same implanted electrode to serve as voltage sensor, while disallowing the sending a stimulus during the rest of the interval between two successive pulses, such that the implanted electrode serves for say, 50 to 100 microseconds as a stimulating electrode and, for the next 5000 to 7000 microseconds of each stimulation cycle, serving as a sensor, to allow sensing of voltage at the vicinity of the stimulation site in the brain, while eliminating the need to implant a separate sensor for voltage sensing in the brain.
 12. As in claim 11, where the electronic switch serves also to change impedance of the implanted electrode from one required when serving as stimulator to another when serving as sensor.
 13. As in claim 1, where the controller device also integrates the information from the various sensors above, and where integration may be performed by a neural network (NN) incorporated in the signal processor.
 14. As in claim 11, where the controller device discriminates between desired motor functions and tremors or other abnormal motor functions in the sensor signals, using the neural network as above. 